WO2013130881A1 - Procédés de production, de modification et d'utilisation de nanoparticules métalliques - Google Patents

Procédés de production, de modification et d'utilisation de nanoparticules métalliques Download PDF

Info

Publication number
WO2013130881A1
WO2013130881A1 PCT/US2013/028422 US2013028422W WO2013130881A1 WO 2013130881 A1 WO2013130881 A1 WO 2013130881A1 US 2013028422 W US2013028422 W US 2013028422W WO 2013130881 A1 WO2013130881 A1 WO 2013130881A1
Authority
WO
WIPO (PCT)
Prior art keywords
triblock copolymer
metallic
metallic nanoparticles
coated metallic
coated
Prior art date
Application number
PCT/US2013/028422
Other languages
English (en)
Inventor
Christopher C. PERRY
Ralph S. KURTI, Jr.
Theodore SABIR
Original Assignee
Loma Linda University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Loma Linda University filed Critical Loma Linda University
Priority to US14/364,274 priority Critical patent/US9370490B2/en
Publication of WO2013130881A1 publication Critical patent/WO2013130881A1/fr
Priority to US15/179,756 priority patent/US20170119686A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/242—Gold; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/245—Bismuth; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/26—Iron; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/34—Copper; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/38—Silver; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6923—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6927—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
    • A61K47/6929—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5192—Processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • B01J13/20—After-treatment of capsule walls, e.g. hardening
    • B01J13/22—Coating
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Definitions

  • Metallic nanoparticles such as, for example, gold nanoparticles (AuNP) have many known and potential uses.
  • the use of metallic nanoparticles is somewhat limited by two disadvantages.
  • Metallic nanoparticles of different sizes and shapes have different properties which limit the use of metallic nanoparticles produced by currently known methods.
  • the modification of the metallic nanoparticles by currently known methods such as, for example, ligating the metallic nanoparticles with organic functional groups, is both time-consuming and complex, making modified metallic nanoparticles produced by currently known methods expensive to produce and, hence, to use.
  • a method for producing triblock copolymer coated metallic nanoparticle seeds which increases the size and shape homogeneity of the triblock copolymer coated metallic nanoparticle seeds, where the triblock copolymer coated metallic nanoparticle seeds comprise a triblock copolymer portion and a metallic portion.
  • the method comprises: a) providing triblock copolymers; b) providing metallic substrate comprising a metal having at least two oxidation states, a lowest oxidation state and a higher oxidation state, where at least some of the metal is in the higher oxidation state; c) making an aqueous solution of the triblock copolymers and water; d) adding a reducing agent to the solution, where the reducing agent reduces the metal in the metallic substrate in the solution from the higher oxidation state to the lowest oxidation state of the metal, or to an oxidation state that is unstable and that reverts to the lowest oxidation state of the metal without further chemical modification; e) adding the metallic substrate to the solution thereby creating a concentration of metallic substrate in the solution; and f) allowing the solution to remain a sufficient time to allow formation of the triblock copolymer coated metallic nanoparticle seeds.
  • the triblock copolymers are selected from the group consisting of one or more than one of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the triblock copolymers comprise F127 (12600).
  • the metal is selected from the group consisting of Ag, Au, Bi, Cu, Fe, Ni, Ti and Zn.
  • the metallic substrate is a salt of the metal.
  • the metallic substrate is selected from the group consisting of AgN0 3 , CuBr 2 , CuCl 2 , CuF 2 , Cul 2 , CuS0 4 and HAuCl 4 .
  • the metallic substrate is HAuCl 4 .
  • the triblock copolymers comprise one or more than one high molecular weight triblock copolymer (MW > 4000).
  • the one or more than one high molecular weight triblock copolymer is selected from the group consisting of one or more than one of P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the water is deionized water.
  • the method further comprises adding one or more than one low molecular weight triblock copolymer (MW ⁇ 2500) to the solution.
  • the one or more than one low molecular weight triblock copolymer added to the solution is selected from the group consisting of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), and a combination of the preceding.
  • the reducing agent is L-ascorbic acid.
  • the reducing agent is an analog of L-ascorbic acid.
  • the analog of L-ascorbic acid is selected from the group consisting of ascorbyl palmitate and magnesium ascorbyl phosphate.
  • the reducing agent is added to the solution in a higher concentration than the concentration of the metal substrate in the solution.
  • the reducing agent is added to the solution at a concentration of at least 1.5 times the concentration of the metal substrate. In one embodiment, the reducing agent is added to the solution at a concentration of at least 2 times the concentration of the metal substrate. In one embodiment, the reducing agent is added to the solution at a concentration of at least 2.5 times the concentration of the metal substrate. In one embodiment, the reducing agent is added to the solution at a concentration of at least 3 times the concentration of the metal substrate.
  • the metallic substrate is selected from the group consisting of AgN0 3 , CuBr 2 , CuCl 2 , CuF 2 , Cul 2 , CuS0 4 and HAuCl 4 . In one embodiment, the metallic substrate is HAuCl 4 . In one embodiment, the method further comprises harvesting the triblock copolymer coated metallic nanoparticle seeds. In one embodiment, the method further comprises characterizing the triblock copolymer coated metallic nanoparticle seeds.
  • a quantity of triblock copolymer coated metallic nanoparticle seeds where the triblock copolymer coated metallic nanoparticle seeds have a median maximum particle diameter size standard deviation of +/- 25 % of the median maximum particle diameter size by electron microscopy.
  • a quantity of triblock copolymer coated metallic nanoparticle seeds where the triblock copolymer coated metallic nanoparticle seeds have a median maximum particle diameter size standard deviation of +/- 20% of the median maximum particle diameter size by electron microscopy.
  • a quantity of triblock copolymer coated metallic nanoparticle seeds where the triblock copolymer coated metallic nanoparticle seeds have a median maximum particle diameter size standard deviation of +/- 15 % of the median maximum particle diameter size by electron microscopy.
  • a quantity of triblock copolymer coated metallic nanoparticle seeds where the triblock copolymer coated metallic nanoparticle seeds have a median maximum particle diameter size standard deviation of +/- 10% of the median maximum particle diameter size by electron microscopy.
  • a quantity of triblock copolymer coated metallic nanoparticle seeds where the triblock copolymer coated metallic nanoparticle seeds have a median maximum particle diameter size standard deviation of+/- 5 % of the median maximum particle diameter size by electron microscopy.
  • the triblock copolymer coated metallic nanoparticle seeds have a median maximum particle diameter size of between 1 nm and 20 nm.
  • the quantity of triblock copolymer coated metallic nanoparticle seeds have a median maximum particle diameter size of between 5 nm and 15 nm.
  • the triblock copolymer coated metallic nanoparticle seeds have a median maximum particle diameter size of between 8 nm and 12 nm.
  • the triblock copolymer coated metallic nanoparticle seeds have a median maximum particle diameter size of 10 nm with a standard deviation of +/- 1 nm by electron microscopy. In one embodiment, the triblock copolymer coated metallic nanoparticle seeds have a number density of between 0.1 x 10 11 particles/mL and 10 x 10 11 particles/mL. In one embodiment, the triblock copolymer coated metallic nanoparticle seeds have a number density of between 0.5 x 10 11 particles/mL and 5 x 10 11 particles/mL. In one embodiment, the triblock copolymer coated metallic nanoparticle seeds have a number density of between 1 x 10 11 particles/mL and 5 x 10 11 particles/mL.
  • the triblock copolymer coated metallic nanoparticle seeds have a number density of 3 x 10 11 particles/mL.
  • the triblock copolymer coated metallic nanoparticle seeds are produced according to a method of the present invention.
  • the triblock copolymer portion of the triblock copolymer coated metallic nanoparticle seeds is selected from the group consisting of one or more than one of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the metallic portion comprises a metal forming the metallic moiety in transition metals and their oxides selected from the group consisting of Ag, Bi 2 0 3 , CuO, Fe x O y , NiO, Ti0 2 and ZnO. In one embodiment, the metallic portion comprises gold.
  • the present invention there is provided method for producing triblock copolymer coated metallic nanoparticles which increases the size and shape homogeneity of the triblock copolymer coated metallic nanoparticles, where the triblock copolymer coated metallic nanoparticles comprise a triblock copolymer portion and a metallic portion.
  • the method comprises: a) providing metallic nanoparticle seeds made according to the present invention, providing triblock copolymers, and providing metallic substrate comprising a metal; b) making a solution of the metallic nanoparticle seeds and the triblock copolymers; c) adding the metallic substrate to the solution; and d) chemically reducing the metallic substrate in the presence of the triblock copolymers and metallic nanoparticle seeds to produce the triblock copolymer coated metallic nanoparticles.
  • the triblock copolymer portion of the triblock copolymer coated metallic nanoparticles is selected from the group consisting of one or more than one of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the triblock copolymer portion of the triblock copolymer coated metallic nanoparticles comprises F127 (12600).
  • the metallic portion comprises a metal forming the metallic moiety in transition metals and their oxides selected from the group consisting of Ag, Bi 2 0 3 , CuO, Fe x O y , NiO, Ti0 2 and ZnO.
  • the metallic portion comprises gold.
  • the triblock copolymers provided are selected from the group consisting of one or more than one of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the triblock copolymers provided comprises F127 (12600).
  • the metal is selected from the group consisting of Ag, Au, Bi, Cu, Fe, Ni, Ti and Zn.
  • the metallic substrate is a salt of the metal.
  • the metallic substrate is selected from the group consisting of AgN0 3 , CuBr 2 , CuCl 2 , CuF 2 , Cul 2 , CuS0 4 and HAuCl 4 .
  • the metallic substrate is HAuCl 4 .
  • the triblock copolymers comprise one or more than one high molecular weight triblock copolymer (MW > 4000).
  • the one or more than one high molecular weight triblock copolymer is selected from the group consisting of one or more than one of P84 (MW 4200), P85(MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the triblock copolymers further comprise one or more than one low molecular weight triblock copolymer (MW ⁇ 2500).
  • the one or more than one low molecular weight triblock copolymer is selected from the group consisting of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), and a combination of the preceding.
  • the method further comprises monitoring the production of the coated metallic nanoparticles.
  • the method further comprises characterizing the triblock copolymer coated gold nanoparticles.
  • a quantity of triblock copolymer coated metallic nanoparticles where the triblock copolymer coated metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 25 % of the median maximum particle diameter size by electron microscopy.
  • a quantity of triblock copolymer coated metallic nanoparticles where the triblock copolymer coated metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 20% of the median maximum particle diameter size by electron microscopy.
  • a quantity of triblock copolymer coated metallic nanoparticles where the triblock copolymer coated metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 15 % of the median maximum particle diameter size by electron microscopy.
  • a quantity of triblock copolymer coated metallic nanoparticles where the triblock copolymer coated metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 10% of the median maximum particle diameter size by electron microscopy.
  • a quantity of triblock copolymer coated metallic nanoparticles where the triblock copolymer coated metallic nanoparticles have a median maximum particle diameter size standard deviation of+/- 5 % of the median maximum particle diameter size by electron microscopy.
  • the triblock copolymer coated metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm.
  • the triblock copolymer coated metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm.
  • the triblock copolymer coated metallic nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm.
  • the triblock copolymer coated metallic nanoparticles have a number density of between 0.1 x 10 10 particles/cm 3 and 10 x 10 10 particles/cm 3 . In one embodiment, the triblock copolymer coated metallic nanoparticles have a number density of between 0.5 x 10 10 particles/cm 3 and 5 x 10 10 particles/cm 3 . In one embodiment, the triblock copolymer coated metallic nanoparticles have a number density of between 1 x 10 10 particles/cm 3 and 5 x 10 10 particles/cm 3 . In one embodiment, the triblock copolymer coated metallic nanoparticles have a number density of 1 x 10 10 particles/cm 3 . In one embodiment, the triblock copolymer coated metallic nanoparticles have a number density of 1 x 10 10 particles/cm 3 . In one embodiment, the triblock copolymer coated metallic
  • the triblock copolymer portion of the triblock copolymer coated metallic nanoparticles is selected from the group consisting of one or more than one of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the metallic portion comprises a metal forming the metallic moiety in transition metals and their oxides selected from the group consisting of Ag, Bi 2 0 3 , CuO, Fe x O y , NiO, Ti0 2 and ZnO. In one embodiment, the metallic portion comprises gold.
  • a method for producing modified metallic nanoparticles comprising: a) providing triblock copolymer coated metallic nanoparticles made according to the present invention; and b) replacing the triblock copolymer portion with the ligand.
  • a method for producing modified metallic nanoparticles where the modified metallic nanoparticles comprise a ligand portion and a metallic portion.
  • the ligand portion comprises a small organic molecule.
  • the ligand portion is selected from the group consisting of one or more than one antibody, metal, peptide, protein, oligonucleotide, thiolated DNA and a combination of the preceding.
  • the metallic portion of the modified metallic nanoparticles comprises gold.
  • a quantity of modified metallic nanoparticles where the modified metallic nanoparticles have a median maximum particle diameter size standard deviation of + /- 25 % of the median maximum particle diameter size by electron microscopy.
  • a quantity of modified metallic nanoparticles where the modified metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 20% of the median maximum particle diameter size by electron microscopy.
  • a quantity of modified metallic nanoparticles where the modified metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 15 % of the median maximum particle diameter size by electron microscopy.
  • a quantity of modified metallic nanoparticles where the modified metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 10% of the median maximum particle diameter size by electron microscopy.
  • a quantity of modified metallic nanoparticles where the modified metallic nanoparticles have a median maximum particle diameter size standard deviation of+/- 5 % of the median maximum particle diameter size by electron microscopy.
  • the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm.
  • the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm.
  • the modified metallic nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm. In one embodiment, the modified metallic nanoparticles have a number density of between 0.1 x 10 10 particles/cm 3 and 10 x 10 10 particles/cm 3 . In one embodiment, the modified metallic nanoparticles have a number density of between 0.5 x 10 10 particles/cm 3 and 5 x 10 10 particles/cm 3 . In one embodiment, the modified metallic nanoparticles have a number density of between 1 x 10 10 particles/cm 3 and 5 x 10 10 particles/cm 3 . In one embodiment, the modified metallic nanoparticles have a number density of 1 x 10 10 particles/cm 3 .
  • the modified metallic nanoparticles are produced according to the method of the present invention.
  • the triblock copolymer portion of the modified metallic nanoparticles is selected from the group consisting of one or more than one of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the metallic portion comprises a metal forming the metallic moiety in transition metals and their oxides selected from the group consisting of Ag, Bi 2 0 3 , CuO, Fe x O y , NiO, Ti0 2 and ZnO.
  • the metallic portion of the modified metallic nanoparticles comprises gold.
  • the method comprises providing the triblock copolymer coated metallic nanoparticles according to the present invention.
  • a method of treating a patient for a condition or disease comprises: a) determining that the patient has a condition or disease suitable for treatment by the administration of triblock copolymer coated metallic nanoparticles; b) providing triblock copolymer coated metallic nanoparticles according to the present invention; and c) administering to the patient one or more than one dose of the triblock copolymer coated metallic nanoparticles by a route, thereby treating the condition or disease.
  • the patient is a human.
  • the one or more than one dose administered is between 0.01 ng and 1 gram.
  • the one or more than one dose administered is between 0.01 ng and 10,000 mg.
  • the one or more than one dose administered is between 1 ng and 10,000 mg. In one embodiment, the one or more than one dose administered is between 0.1 mg and 10,000 mg. In one embodiment, the one or more than one dose is a plurality of doses. In one embodiment, the plurality of doses is two doses. In one embodiment, the plurality of doses is three doses. In one embodiment, the plurality of doses is four doses. In one embodiment, the plurality of doses is more than four doses. In one embodiment, the plurality of doses is administered between one hour and seventy-two hours apart. In one embodiment, the plurality of doses is administered between one hour and thirty-six hours apart.
  • the plurality of doses is administered between one hour and twenty-four hours apart.
  • the route is selected from the group consisting of intrarectal, intramuscular, intraperitoneal, intrathecal, intravenous and oral.
  • the condition or disease is cancer and administering the triblock copolymer coated metallic nanoparticles decreases the toxicity of radiotherapy being used to treat the cancer.
  • the ligand portion of the triblock copolymer coated metallic nanoparticles is a delivery vehicle for biologically active agents.
  • determining that the patient has a condition or disease suitable for treatment by the administration of the triblock copolymer coated metallic nanoparticles comprises diagnosing the patient with a condition or disease suitable for treatment by the method.
  • diagnosing the patient comprises performing one or more than one of action selected from the group consisting of performing a physical examination, performing a noninvasive imaging examination, and identifying one or more than one marker for the condition or disease in the blood or other body fluid of the patient.
  • identifying the patient comprises consulting patient records to determine if the patient has a condition or disease suitable for treatment by the method.
  • the method comprises providing the modified metallic nanoparticles according to the present invention.
  • a method of treating a patient for a condition or disease comprises: a) determining that the patient has a condition or disease suitable for treatment by the administration of modified metallic nanoparticles; b) providing modified metallic nanoparticles according to the present invention; and c) administering to the patient one or more than one dose of the triblock copolymer coated metallic nanoparticles by a route, thereby treating the condition or disease.
  • the patient is a human.
  • the one or more than one dose administered is between 0.01 ng and 1 gram.
  • the one or more than one dose administered is between 0.01 ng and 10,000 mg.
  • the one or more than one dose administered is between 1 ng and 10,000 mg. In one embodiment, the one or more than one dose administered is between 0.1 mg and 10,000 mg. In one embodiment, the one or more than one dose administered is a plurality of doses. In one embodiment, the plurality of doses is two doses. In one embodiment, the plurality of doses is three doses. In one embodiment, the plurality of doses is four doses. In one embodiment, the plurality of doses is more than four doses. In one embodiment, the plurality of doses is administered between one hour and seventy-two hours apart. In one embodiment, the plurality of doses is administered between one hour and thirty-six hours apart.
  • the plurality of doses is administered between one hour and twenty-four hours apart.
  • the route is selected from the group consisting of intrarectal, intramuscular, intraperitoneal, intrathecal, intravenous and oral.
  • the condition or disease is cancer and administering the triblock copolymer coated metallic nanoparticles decreases the toxicity of radiotherapy being used to treat the cancer.
  • the ligand portion of the triblock copolymer coated metallic nanoparticles is a delivery vehicle for biologically active agents.
  • the patient has a condition or disease suitable for treatment by the administration of the triblock copolymer coated metallic nanoparticles and the method further comprises diagnosing the patient with a condition or disease suitable for treatment by the method.
  • diagnosing the patient comprises performing one or more than one of action selected from the group consisting of performing a physical examination, performing a non-invasive imaging examination, and identifying one or more than one marker for the condition or disease in the blood or other body fluid of the patient.
  • identifying the patient comprises consulting patient records to determine if the patient has a condition or disease suitable for treatment by the method.
  • a pharmaceutical suitable for treating a patient with a condition or disease comprises triblock copolymer coated metallic nanoparticles according to the present invention.
  • the pharmaceutical further comprises one or more than one substance selected from the group consisting of a binder, a coloring chemical and a flavoring chemical.
  • a pharmaceutical suitable for treating a patient with a condition or disease comprising modified metallic nanoparticles according to the present invention.
  • the pharmaceutical further comprises one or more than one substance selected from the group consisting of a binder, a coloring chemical and a flavoring chemical. DESCRIPTION
  • a method for producing triblock copolymer-coated metallic nanoparticle seeds which increases the size and shape homogeneity of the triblock copolymer coated metallic nanoparticle seeds compared to triblock copolymer-coated metallic nanoparticles produced by currently known methods, where the triblock copolymer-coated metallic nanoparticle seeds comprise a triblock copolymer portion and a metallic portion.
  • the metallic portion of the triblock copolymer-coated metallic nanoparticle seeds comprises gold.
  • a quantity of triblock copolymer-coated metallic nanoparticle seeds having a narrow particle size distribution.
  • the triblock copolymer-coated metallic nanoparticle seeds having the narrow particle size distribution are produced according to the method for producing triblock copolymer-coated metallic nanoparticle seeds according to the present invention.
  • a method for producing triblock copolymer-coated metallic nanoparticles which increases the size and shape homogeneity of the triblock copolymer-coated metallic nanoparticles as compared to triblock copolymer-coated metallic nanoparticles produced by currently known methods, where the triblock copolymer-coated metallic nanoparticles comprise a triblock copolymer portion and a metallic portion.
  • the method comprises providing triblock copolymer-coated metallic nanoparticle seeds according to the present invention.
  • the metallic portion of the triblock copolymer-coated metallic nanoparticles comprises gold.
  • a quantity of triblock copolymer-coated metallic nanoparticles having a narrow particle size distribution there is provided a method for producing modified metallic nanoparticles which increases the size and shape homogeneity of the modified metallic nanoparticles as compared to modified metallic nanoparticles produced by currently known methods, where the modified metallic nanoparticles comprise a ligand portion and a metallic portion. The method comprises providing triblock copolymer-coated metallic nanoparticles made according to the present invention.
  • the ligand portion of the modified metallic nanoparticles is selected from the group consisting of one or more than one antibody, metal, peptide, protein, oligonucleotide, thiolated DNA and a combination of the preceding.
  • the metallic portion of the modified metallic nanoparticles comprises gold.
  • a quantity of modified metallic nanoparticles having a narrow particle size distribution there is provided a method of using triblock copolymer-coated metallic nanoparticles or modified metallic nanoparticles, where the method comprises providing triblock copolymer- coated metallic nanoparticles or modified metallic nanoparticles produced according to the present invention.
  • the method of using comprises treating a patient for a condition or disease. In another embodiment, the method of using comprises decreasing the potential toxicity of radiation administered to the patient.
  • a pharmaceutical suitable for treating a patient with a condition or disease comprises triblock copolymer-coated metallic nanoparticles produced according to the method for producing triblock copolymer-coated metallic nanoparticles of the present invention. In another embodiment, the pharmaceutical comprises modified metallic nanoparticles produced according to the method for producing modified metallic nanoparticles of the present invention. The methods, triblock copolymer-coated metallic nanoparticle seeds, triblock copolymer-coated metallic nanoparticles, modified metallic nanoparticles and pharmaceuticals will now be disclosed in detail.
  • gold is used as an example of the metallic portion of the triblock copolymer-coated metallic nanoparticle seeds, the triblock copolymer-coated metallic nanoparticles, the modified metallic nanoparticles and the pharmaceuticals according to the present invention; however, except where the context requires otherwise, the metallic portion of the triblock copolymer-coated metallic nanoparticle seeds, the triblock copolymer-coated metallic nanoparticles, the modified metallic nanoparticles and the pharmaceuticals according to the present invention can be metals other than gold, such as, for example, metals forming the metallic moiety in transition metals and their oxides selected from the group consisting of Ag, Bi 2 0 3 , CuO, Fe x O y , NiO, Ti0 2 and ZnO, as will be understood by those with skill in the art with respect to this disclosure.
  • triblock copolymers means a central hydrophobic chain of polyoxypropylene (poly(propylene oxide); PO) flanked by two hydrophilic chains of poly oxy ethylene (poly(ethylene oxide); EO), and are also known as poloxamers, and under the commercial names KolliphorTM ( BASF SE, Ludwigshafen am Rhein, Germany); Pluronic ® (BASF Corporation, North Mount Olive, NJ US) and
  • modified metallic nanoparticles means triblock copolymer-coated metallic nanoparticles produced according to the present method where the triblock copolymer portion has been replaced with a ligand active for an intended purpose, such as, for example, a moiety selected from the group consisting of one or more than one antibody, metal, peptide, protein, oligonucleotide, thiolated DNA and a combination of the preceding.
  • a ligand active for an intended purpose such as, for example, a moiety selected from the group consisting of one or more than one antibody, metal, peptide, protein, oligonucleotide, thiolated DNA and a combination of the preceding.
  • median maximum particle diameter size means that 50% of the sample has a smaller maximum particle diameter and 50% of the sample has a larger maximum particle diameter as measured by electron microscopy.
  • a method for producing triblock copolymer-coated metallic nanoparticle seeds which increases the size and shape homogeneity of the triblock copolymer-coated metallic nanoparticle seeds compared to triblock copolymer-coated metallic nanoparticles produced by currently known methods, where the triblock copolymer-coated metallic nanoparticle seeds comprise a triblock copolymer portion and a metallic portion.
  • the method comprises: a) providing triblock copolymers; b) providing metallic substrate comprising a metal having at least two oxidation states, a lowest oxidation state and a higher oxidation state, where at least some of the metal is in the higher oxidation state; c) making an aqueous solution of the triblock copolymers and water; d) adding a reducing agent to the solution, where the reducing agent reduces the metal in the metallic substrate in the solution from the higher oxidation state to the lowest oxidation state of the metal, or to an oxidation state that is unstable and that reverts to the lowest oxidation state of the metal without further chemical modification; e) adding the metallic substrate to the solution thereby creating a concentration of metallic substrate in the solution; and f) allowing the solution to remain a sufficient time to allow formation of the triblock copolymer-coated metallic nanoparticle seeds.
  • the metal in a metallic salt in the solution is gold and the reducing agent is L-ascorbic acid, where the electrode potential dihydroascorbic
  • the acid/L-ascorbic acid is about 0.2 V for pH values ⁇ 4.
  • the reducing agent is an analog of L-ascorbic acid.
  • the analog of L-ascorbic acid is selected from the group consisting of ascorbyl palmitate and magnesium ascorbyl phosphate.
  • the method for producing triblock copolymer-coated metallic nanoparticle seeds comprises providing triblock copolymers.
  • the triblock copolymers are selected from the group consisting of one or more than one of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the triblock copolymers comprises F127 (12600).
  • the triblock copolymers provided can be made according to techniques known to those with skill in the art, or can be purchased from a variety of commercially available sources, such as, for example, Sigma-Aldrich, Milwaukee, WI US.
  • the method further comprises providing metallic substrate comprising a metal having at least two oxidation states, a lowest oxidation state and a higher oxidation state, where at least some of the metal is in the higher oxidation state.
  • the metal is selected from the group consisting of Ag, Au, Bi, Cu, Fe, Ni, Ti and Zn.
  • the metallic substrate is a salt of the metal.
  • the metallic substrate is selected from the group consisting of AgN0 3 , CuBr 2 , CuCl 2 , CuF 2 , Cul 2 , CuS0 4 and HAuCl 4 .
  • the metallic substrate is HAuCl 4 .
  • the metallic substrate provided can be purchased commercially, such as, for example, from Sigma- Aldrich, Milwaukee, WI US. In another embodiment, the metallic substrate is made according to techniques known to those with skill in the art.
  • the method comprises making an aqueous solution of the provided triblock copolymers and water.
  • the provided triblock copolymers comprise one or more than one high molecular weight triblock copolymer (MW > 4000).
  • the one or more than one high molecular weight triblock copolymer is selected from the group consisting of one or more than one of P84 (MW 4200), P85(MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the solution is made by adding the triblock copolymers to deionized water.
  • this solution can be made by adding the high molecular weight triblock copolymers to deionized water (Milli-Q water; Millipore, Billerica, MA US) to give a final concentration in (weight/volume) % of between 1 % (lg/100 mL) and 5 % (5g/100 mL).
  • the high molecular weight triblock copolymer is F127 (MW 12600).
  • the method further comprises adding one or more than one low molecular weight triblock copolymer (MW ⁇ 2500) to the solution.
  • the combination of high molecular weight triblock copolymers and low molecular weight triblock copolymers advantageously produces an additional level of control over the triblock copolymer phase behavior, as will be understood by those with skill in the art with respect to this disclosure.
  • the one or more than one low molecular weight triblock copolymer added to the solution is selected from the group consisting of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), and a combination of the preceding.
  • the solution can be made using F68 as the high molecular weight triblock copolymer and L31 as the low molecular weight triblock copolymer.
  • the solution can be made by dissolving 10 mL of 50% w/v
  • the cloud point (CP) (where the solution phase separates of stock) can be reduced from above 100°C for aqueous F68 binary mixtures to about 30 °C for aqueous L31/F68 ternary mixtures.
  • the method comprises adding a reducing agent to the solution, where the reducing agent reduces the metal in the metallic substrate in the solution from the higher oxidation state to the lowest oxidation state of the metal, or to an oxidation state that is unstable and that reverts to the lowest oxidation state of the metal without further chemical modification.
  • the metal in the metallic portion is gold
  • the reducing agent has a standard electrode potential that is weakly positive and less than the electrode potential for
  • the reducing agent is L-ascorbic acid (that has an electrode potential dihydroascorbic acid/L-ascorbic acid is about 0.2 V for pH values ⁇ 4).
  • the reducing agent is an analog of L-ascorbic acid.
  • the analog of L-ascorbic acid is selected from the group consisting of ascorbyl palmitate and magnesium ascorbyl phosphate.
  • the reducing agent is added to the solution in a higher
  • the reducing agent is added to the solution at a concentration of at least 1.5 times the concentration of the metal substrate. In one embodiment, the reducing agent is added to the solution at a concentration of at least 2 times the concentration of the metal substrate. In one embodiment, the reducing agent is added to the solution at a concentration of at least 2.5 times the concentration of the metal substrate. In one embodiment, the reducing agent is added to the solution at a concentration of at least 3 times the concentration of the metal substrate. In one embodiment, the reducing agent is added to the solution at a concentration of 5 mM.
  • the method comprises adding the metallic substrate to the solution, thereby creating a concentration of metallic substrate in the solution.
  • the metallic substrate is selected from the group consisting of AgN0 3 , CuBr 2 , CuCl 2 , CuF 2 , Cul 2 , CuS0 4 and HAuCl 4 .
  • the metallic substrate is HAuCl 4 .
  • the metallic substrate is HAuCl 4 .
  • the metallic substrate is 0.2 mM HAuCl 4 .
  • 0.2 mM HAuC14 was added to 5 mM of the aqueous solution of the triblock copolymer solution and reducing agent.
  • the method comprises allowing the solution to remain a sufficient time to allow formation of the triblock copolymer-coated metallic nanoparticle seeds, such as, for example, until the solution changed color indicting completion of the formation.
  • the method further comprises harvesting the triblock copolymer-coated metallic nanoparticle seeds.
  • triblock copolymer-coated metallic nanoparticle seeds made as disclosed were harvested by first washing by centrifugation (17,900 g; 5 min) and suspended in water in preparation for characterization.
  • the method further comprises characterizing the triblock copolymer-coated gold nanoparticle seeds produced according to the present invention.
  • characterizing comprises measuring the size of the triblock copolymer-coated metallic nanoparticle seeds using scanning transmission electron microscopy using techniques known to those with skill in the art, as will be understood by those with skill in the art with respect to this disclosure.
  • the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size standard deviation of + /- 25 % of the median maximum particle diameter size by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size standard deviation of +/- 20% of the median maximum particle diameter size by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size standard deviation of +/- 15 % of the median maximum particle diameter size by electron microscopy.
  • the triblock copolymer- coated metallic nanoparticle seeds have a median maximum particle diameter size standard deviation of +/- 10% of the median maximum particle diameter size by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size standard deviation of +/- 5 % of the median maximum particle diameter size by electron microscopy. In one embodiment, the triblock copolymer- coated metallic nanoparticle seeds have a median maximum particle diameter size of between 1 nm and 20 nm with a standard deviation of less than +/- 25 % by electron microscopy.
  • the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 1 nm and 20 nm with a standard deviation of less than +/- 20% by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 1 nm and 20 nm with a standard deviation of less than +/- 15 % by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 1 nm and 20 nm with a standard deviation of less than +/- 10% by electron microscopy.
  • the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 1 nm and 20 nm with a standard deviation of less than +/- 5 % by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 5 nm and 15 nm with a standard deviation of less than +/- 25 % by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 5 nm and 15 nm with a standard deviation of less than +/- 20% by electron microscopy.
  • the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 5 nm and 15 nm with a standard deviation of less than +/- 15 % by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 5 nm and 15 nm with a standard deviation of less than +/- 10% by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 5 nm and 15 nm with a standard deviation of less than +/- 5 % by electron microscopy.
  • the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 8 nm and 12 nm with a standard deviation of less than +/- 25 % by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 8 nm and 12 nm with a standard deviation of less than +/- 20% by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 8 nm and 12 nm with a standard deviation of less than +/- 15 % by electron microscopy.
  • the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 8 nm and 12 nm with a standard deviation of less than +/- 10% by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of between 8 nm and 12 nm with a standard deviation of less than +/- 5 % by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a median maximum particle diameter size of 10 nm with a standard deviation of +/- 1 nm by electron microscopy.
  • the triblock copolymer-coated metallic nanoparticle seeds have a number density of between 0.1 x 10 11 particles/mL and 10 x 10 11 particles/mL. In another embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a number density of between 0.5 x 10 11 particles/mL and 5 x 10 11 particles/mL. In another embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a number density of between 1 x 10 11 particles/mL and 5 x 10 11 particles/mL. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds have a number density of 3 x 10 11 particles/mL. In one embodiment, the triblock copolymer-coated metallic nanoparticle seeds having the narrow particle size distribution according to the present invention are produced according to the method for producing triblock copolymer-coated metallic nanoparticle seeds according to the present invention.
  • the triblock copolymer portion of the triblock copolymer-coated metallic nanoparticle seeds is selected from the group consisting of one or more than one of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the triblock copolymer portion of the triblock copolymer-coated metallic nanoparticle seeds comprises F127 (12600).
  • the metallic portion comprises a metal forming the metallic moiety in transition metals and their oxides selected from the group consisting of Ag, Bi 2 0 3 , CuO, Fe x O y , NiO, Ti0 2 and ZnO.
  • the metallic portion of the triblock copolymer-coated metallic nanoparticle seeds comprises gold.
  • a method for producing triblock copolymer-coated metallic nanoparticles which increases the size and shape homogeneity of the triblock copolymer-coated metallic nanoparticles as compared to triblock copolymer-coated metallic nanoparticles produced by currently known methods, where the triblock copolymer-coated metallic nanoparticles comprise a triblock copolymer portion and a metallic portion.
  • the method for producing triblock copolymer-coated metallic nanoparticles comprises: a) providing metallic nanoparticle seeds made according to the present invention, providing triblock copolymers, and providing metallic substrate
  • the triblock copolymer portion of the triblock copolymer-coated metallic nanoparticles is selected from the group consisting of one or more than one of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the triblock copolymer portion of the triblock copolymer-coated metallic nanoparticles comprises F127 (12600).
  • the metallic portion comprises a metal forming the metallic moiety in transition metals and their oxides selected from the group consisting of Ag, Bi 2 0 3 , CuO, Fe x O y , NiO, Ti0 2 and ZnO.
  • the metallic portion of the triblock copolymer-coated metallic nanoparticle seeds comprises gold.
  • the method for producing triblock copolymer-coated metallic nanoparticles comprises providing triblock copolymer-coated metallic nanoparticle seeds produced according to the present invention.
  • the method for producing triblock copolymer-coated metallic nanoparticles comprises providing triblock copolymers.
  • the triblock copolymers provided are selected from the group consisting of one or more than one of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the triblock copolymers provided comprises F127 (12600).
  • the triblock copolymers provided can be made according to techniques known to those with skill in the art, or can be purchased from a variety of commercially available sources, such as, for example, Sigma-Aldrich, Milwaukee, WI US.
  • the method further comprises providing metallic substrate comprising a metal.
  • the metal is selected from the group consisting of Ag, Au, Bi, Cu, Fe, Ni, Ti and Zn.
  • the metallic substrate is a salt of the metal.
  • the metallic substrate is selected from the group consisting of AgN0 3 , CuBr 2 , CuCl 2 , CuF 2 , Cul 2 , CuS0 4 and HAuCl 4 .
  • the metallic substrate is HAuCl 4 .
  • the metallic substrate provided can be purchased commercially, such as, for example, from Sigma-Aldrich, Milwaukee, WI US. In another embodiment, the metallic substrate is made according to techniques known to those with skill in the art.
  • the method comprises making a solution of the metallic nanoparticle seeds, the triblock copolymers, and the metallic substrate.
  • making the solution comprises adding the metallic nanoparticle seeds made according to the present invention, and one or more than one high molecular weight triblock copolymer (MW > 4000), to water.
  • the one or more than one high molecular weight triblock copolymer is selected from the group consisting of one or more than one of P84 (MW 4200), P85(MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108
  • the water is deionized water.
  • the solution can be made by dissolving the high molecular weight triblock copolymers in deionized water (Milli-Q water; Millipore, Billerica, MA US) to give a final concentration in (weight/ volume) % of between 1 % (lg/100 mL) and 5 % (5g/100 mL).
  • metallic nanoparticle seeds are added to the solution to a final concentration of between 0.1 nM to 1 nM, such as, for example, adding 100 ⁇ . of metallic nanoparticle seeds to 900 ⁇ . of solution to make 1 mL solution.
  • the method further comprises adding one or more than one low molecular weight triblock copolymer (MW ⁇ 2500) to the solution.
  • the combination of high molecular weight triblock copolymers and low molecular weight triblock copolymers advantageously produce an additional level of control over the triblock copolymer phase behavior, as will be understood by those with skill in the art with respect to this disclosure.
  • the one or more than one low molecular weight triblock copolymer added to the solution is selected from the group consisting of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), and a combination of the preceding.
  • the solution with the low molecular weight triblock copolymers can be made using F68 as the high molecular weight triblock copolymer and L31 as the low molecular weight triblock copolymer.
  • the solution can be made by dissolving 10 mL of 50% w/v (50g/100 mL) F68 and 10 mL L31 in 100 mL of deionized water (Milli-Q water; Millipore, Billerica, MA US) to give a final concentration of 8 mM L31 and 4 mM F68. This mixture corresponds to an EO:PO molar ratio of about 0.7.
  • metallic nanoparticle seeds are added to the solution to a final concentration of 0.1 nM to 1 nM, such as, for example, adding 100 of metallic nanoparticle seeds to 900 of solution to make 1 mL solution.
  • the cloud point (CP) (where the solution phase separates of stock) can be reduced from above 100°C for aqueous F68 binary mixtures to about 30 °C for aqueous L31/F68 ternary mixtures. The solution was incubated at 25 °C for about 15 minutes.
  • the method comprises adding the metallic substrate to the solution.
  • 100 mM HAuCl 4 was added to the solution to give a final Au(III) concentration of 1 mM, thereby producing the triblock copolymer-coated metallic nanoparticles.
  • the method comprises chemically reducing the metallic substrate in the presence of the triblock copolymers and metallic nanoparticle seeds, thereby producing the triblock copolymer-coated metallic nanoparticles.
  • Increasing the seed concentration reduced the average particle size.
  • the triblock copolymer- coated metallic nanoparticles produced were heterogeneous.
  • An examination of the volume weighted DLS particle size distribution and electron microscopy showed that increasing the seed concentration decreases the mean hydrodynamic diameters from (1370 + 290) to (86 + 12) nm in the larger triblock copolymer-coated metallic nanoparticles population.
  • the method further comprises monitoring the production of the coated metallic nanoparticles.
  • monitoring is performed by observing the changes in the absorption spectra using a UV-vis spectrometer (such as, for example, a Varian Cary 300, LabWrench, Midland, ON Canada) fitted with temperature control at 25 + 1 °C.
  • the growth kinetics within the first 30 minutes of growth are monitored by UV-vis spectroscopy by monitoring the evolution of the precursor and gold nanoparticles peaks at 320 and 540 nm, respectively.
  • the AuCl 4 concentration is estimated from the absorption bands by the use of extinction coefficients: 9823 M “1 cm “1 and 5400 M “1 cm “1 , at 240 and 320 nm, respectively.
  • Dynamic light scattering (DLS) measurements are made (such as, for example, using a model NICOMP 370 submicron particle sizer, Particle Sizing Systems, Santa Barbara, CA US) at a He-Ne laser wavelength of 632 nm with a power output of 60 mW.
  • samples are centrifuged (10,600 x g) to remove excess surfactant and suspended in water.
  • the method further comprises characterizing the triblock copolymer-coated gold nanoparticles produced according to the present invention.
  • characterizing comprises measuring the size of the triblock copolymer-coated metallic nanoparticles using scanning transmission electron microscopy using techniques known to those with skill in the art, as will be understood by those with skill in the art with respect to this disclosure.
  • characterization using scanning transmission electron microscopy comprises preparing the samples by centrifuging (10,600 x g) the samples twice to remove excess polymer, and then suspending the centrifuged sample in water. Next, a drop of the suspended sample is mounted on a carbon-coated Cu grid (such as, for example, 200 mesh, Ted Pella, Inc.
  • characterizing comprises imaging the triblock copolymer-coated metallic nanoparticles using atomic force microscopy (AFM), using techniques known to those with skill in the art, as will be understood by those with skill in the art with respect to this disclosure.
  • FEM field emission scanning electron microscopy
  • Automated feedback parameter optimization is achieved using
  • the Peak Force Tapping ® mode modulates the cantilever at ca 2 kHz at each pixel of the image where the feedback is based on the interaction force each time the tip taps the sample.
  • the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 25 % of the median maximum particle diameter size by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 20% of the median maximum particle diameter size by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 15 % of the median maximum particle diameter size by electron microscopy.
  • the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 10% of the median maximum particle diameter size by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 5 % of the median maximum particle diameter size by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm with a standard deviation of +/- 25 % by electron microscopy.
  • the triblock copolymer- coated metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm with a standard deviation of +/- 20% by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm with a standard deviation of +/- 15 % by electron microscopy. In one embodiment, the triblock copolymer-coated metallic
  • the nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm with a standard deviation of +/- 10% by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm with a standard deviation of +/- 5 % by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm with a standard deviation of +/- 25 % by electron microscopy.
  • the triblock copolymer- coated metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm with a standard deviation of +/- 20% by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm with a standard deviation of +/- 15 % by electron microscopy. In one embodiment, the triblock copolymer-coated metallic
  • the nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm with a standard deviation of +/- 10% by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm with a standard deviation of +/- 5 % by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm with a standard deviation of +/- 25 % by electron microscopy.
  • the triblock copolymer- coated metallic nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm with a standard deviation of +/- 20% by electron microscopy. In one embodiment, the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm with a standard deviation of +/- 15 % by electron microscopy. In one embodiment, the triblock copolymer-coated metallic
  • the nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm with a standard deviation of +/- 10% by electron microscopy.
  • the triblock copolymer-coated metallic nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm with a standard deviation of + /- 5 % by electron microscopy.
  • the number density of the triblock copolymer-coated metallic nanoparticles is between 0.1 x 10 10 particles/cm 3 and 10 x 10 10 particles/cm 3 .
  • the number density of the triblock copolymer-coated metallic nanoparticles is between 0.5 x 10 10 particles/cm 3 and 5 x 10 10 particles/cm 3 . In one embodiment, the number density of the triblock copolymer-coated metallic nanoparticles is between 1 x 10 10 particles/cm 3 and 5 x 10 10 particles/cm 3 . In one embodiment, the number density of the triblock copolymer-coated metallic nanoparticles is 1 x 10 10 particles/cm 3 . In one
  • the triblock copolymer-coated metallic nanoparticles having the narrow particle size distribution are produced according to the method for producing triblock copolymer- coated metallic nanoparticles according to the present invention.
  • the triblock copolymer portion of the triblock copolymer-coated metallic nanoparticles is selected from the group consisting of one or more than one of L31 (MW 1100), L43 (MW 1850), L44 (MW 2200), L62 (MW 2500), P84 (MW 4200), P85 (MW 4600), P123 (MW 5760), F68 (MW 8400), F88 (MW 11400), F127 (MW 12600), F108 (MW 14600), and a combination of the preceding.
  • the triblock copolymer portion of the triblock copolymer-coated metallic nanoparticles comprises F127 (12600).
  • the metallic portion comprises a metal forming the metallic moiety in transition metals and their oxides selected from the group consisting of Ag, Bi 2 0 3 , CuO, Fe x O y , NiO, Ti0 2 and ZnO.
  • the metallic portion of the triblock copolymer-coated metallic nanoparticles comprises gold.
  • the modified metallic nanoparticles comprise a ligand portion and a metallic portion.
  • the ligand portion comprises a small organic molecule.
  • the ligand portion is selected from the group consisting of one or more than one antibody, metal, peptide, protein, oligonucleotide, thiolated DNA and a combination of the preceding; however, other ligand portions can be used, as will be understood by those with skill in the art with respect to this disclosure.
  • the metallic portion of the modified metallic nanoparticles comprises gold.
  • the method comprises providing triblock copolymer-coated metallic nanoparticles according to the present invention.
  • the method comprises replacing the triblock copolymer portion with the ligand according to techniques known to those with skill in the art.
  • replacing the triblock copolymer portion with the ligand triblock copolymer portion can comprise one or more than one technique selected from the group consisting of in-situ interfacial reaction, overlayer growth and surface overlayer exchange, though any other suitable method can be used as will be understood by those with skill in the art with respect to this disclosure.
  • the modified metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 25 % of the median maximum particle diameter size by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 20% of the median maximum particle diameter size by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 15 % of the median maximum particle diameter size by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 10% of the median maximum particle diameter size by electron microscopy.
  • the modified metallic nanoparticles have a median maximum particle diameter size standard deviation of +/- 5 % of the median maximum particle diameter size by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm with a standard deviation of +/- 25 % by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm with a standard deviation of +/- 20% by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm with a standard deviation of +/- 15 % by electron microscopy.
  • the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm with a standard deviation of +/- 10% by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 300 nm with a standard deviation of +/- 5 % by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm with a standard deviation of +/- 25 % by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm with a standard deviation of +/- 20% by electron microscopy.
  • the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm with a standard deviation of +/- 15 % by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm with a standard deviation of +/- 10% by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 30 nm and 100 nm with a standard deviation of +/- 5 % by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm with a standard deviation of + /- 25 % by electron microscopy.
  • the modified metallic nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm with a standard deviation of +/- 20% by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm with a standard deviation of +/- 15 % by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm with a standard deviation of +/- 10% by electron microscopy. In one embodiment, the modified metallic nanoparticles have a median maximum particle diameter size of between 40 nm and 60 nm with a standard deviation of +/- 5 % by electron microscopy.
  • the number density of the modified metallic nanoparticles is between 0.1 x 10 10 particles/cm 3 and 10 x 10 10 particles/cm 3 . In one embodiment, the number density of the modified metallic nanoparticles is between 0.5 x 10 10 particles/cm 3 and 5 x 10 10 particles/cm 3 . In one embodiment, the number density of the modified metallic nanoparticles is between 1 x 10 10 particles/cm 3 and 5 x 10 10 particles/cm 3 . In one embodiment, the number density of the modified metallic nanoparticles is between 1 x 10 10 particles/cm 3 . In one embodiment, the modified metallic nanoparticles having the narrow particle size distribution are produced according to the method for producing modified metallic nanoparticles according to the present invention.
  • a method of using triblock copolymer-coated metallic nanoparticles where the method comprises providing the triblock copolymer-coated metallic nanoparticles according to the present invention.
  • a method of using modified metallic nanoparticles where the method comprises providing the modified metallic nanoparticles according to the present invention.
  • a method of treating a patient for a condition or disease comprises, first determining that the patient has a condition or disease suitable for treatment by the administration of the triblock copolymer-coated metallic nanoparticles. Next, the method comprises providing triblock copolymer-coated metallic nanoparticles according to the present invention. Then, the method comprises administering to the patient one or more than one dose of the triblock copolymer-coated metallic nanoparticles by a route, thereby treating the condition or disease.
  • the patient is a human.
  • the one or more than one dose administered is between 0.01 ng and 1 gram.
  • the one or more than one dose administered is between 0.01 ng and 10,000 mg. In another embodiment, the one or more than one dose administered is between 1 ng and 10,000 mg. In another embodiment, the one or more than one dose administered is between 0.1 mg and 10,000 mg. In one embodiment, the one or more than one dose administered is a plurality of doses. In one embodiment, the plurality of doses is two doses. In another embodiment, the plurality of doses is three doses. In another embodiment, the plurality of doses is four doses. In another embodiment, the plurality of doses is more than four doses. In one embodiment, the plurality of doses is administered between one hour and seventy-two hours apart.
  • the plurality of doses is administered between one hour and thirty-six hours apart. In another embodiment, the plurality of doses is administered between one hour and twenty-four hours apart.
  • the route is selected from the group consisting of intrarectal, intramuscular, intraperitoneal, intrathecal, intravenous and oral.
  • the condition or disease is cancer and administering the triblock copolymer- coated metallic nanoparticles decreases the toxicity of radiotherapy being used to treat the cancer.
  • the ligand portion of the triblock copolymer-coated metallic nanoparticles is a delivery vehicle for biologically active agents.
  • determining that the patient has a condition or disease suitable for treatment by the administration of the triblock copolymer-coated metallic nanoparticles comprises diagnosing the patient with a condition or disease suitable for treatment by the present method.
  • diagnosing the patient comprises performing one or more than one of action selected from the group consisting of performing a physical examination, performing a noninvasive imaging examination (such as magnetic resonance imaging, computerized
  • identifying the patient comprises consulting patient records to determine if the patient has a condition or disease suitable for treatment by the present method.
  • a method of treating a patient for a condition or disease comprises, first providing modified metallic nanoparticles according to the present invention. Next, the method comprises determining that the patient has a condition or disease suitable for treatment by the administration of the modified metallic nanoparticles. Then, the method comprises administering to the patient one or more than one dose of the modified metallic nanoparticles by a route, thereby treating the condition or disease.
  • the patient is a human.
  • the one or more than one dose administered is between 0.01 ng and 1 gram. In another embodiment, the one or more than one dose administered is between 0.01 ng and 10,000 mg.
  • the one or more than one dose administered is between 1 ng and 10,000 mg. In another embodiment, the one or more than one dose administered is between 0.1 mg and 10,000 mg. In one embodiment, the one or more than one dose administered is a plurality of doses. In one embodiment, the plurality of doses is two doses. In another embodiment, the plurality of doses is three doses. In another embodiment, the plurality of doses is four doses. In another embodiment, the plurality of doses is more than four doses. In one embodiment, the plurality of doses is administered between one hour and seventy-two hours apart. In another embodiment, the plurality of doses is administered between one hour and thirty-six hours apart.
  • the plurality of doses is administered between one hour and twenty-four hours apart.
  • the route is selected from the group consisting of intrarectal, intramuscular, intraperitoneal, intrathecal, intravenous and oral.
  • the condition or disease is cancer and administering the modified metallic nanoparticles decreases the toxicity of radiotherapy being used to treat the cancer.
  • the ligand portion of the modified metallic nanoparticles is a delivery vehicle for biologically active agents.
  • the ligand portion of the modified metallic nanoparticles is N-caproyl-penta- arginine amide (Cap-R 5 -NH 2 ) (fatty acid) terminated peptide.
  • determining that the patient has a condition or disease suitable for treatment by the administration of the modified metallic nanoparticles comprises diagnosing the patient with a condition or disease suitable for treatment by the present method.
  • diagnosing the patient comprises performing one or more than one of action selected from the group consisting of performing a physical examination, performing a non-invasive imaging examination (such as magnetic resonance imaging, computerized tomography and
  • identifying the patient comprises consulting patient records to determine if the patient has a condition or disease suitable for treatment by the present method.
  • a pharmaceutical suitable for treating a patient with a condition or disease in one embodiment, there is provided a pharmaceutical suitable for treating a patient with a condition or disease.
  • the pharmaceutical comprises triblock copolymer-coated metallic nanoparticles according to the present invention.
  • the pharmaceutical comprises modified metallic nanoparticles according to the present invention.
  • the pharmaceutical additionally comprises one or more than one substance selected from the group consisting of a binder, a coloring chemical and a flavoring chemical, as will be understood by those with skill in the art with respect to this disclosure.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nanotechnology (AREA)
  • Organic Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Ceramic Engineering (AREA)
  • Immunology (AREA)
  • Powder Metallurgy (AREA)
  • Manufacture Of Metal Powder And Suspensions Thereof (AREA)

Abstract

La présente invention concerne un procédé de production de germes de nanoparticules métalliques enrobées d'un copolymère tribloc qui accroît l'homogénéité en taille et en forme des germes de nanoparticules métalliques enrobées d'un copolymère tribloc ; une quantité de germes de nanoparticules métalliques enrobées d'un copolymère tribloc ; un procédé de production de nanoparticules métalliques enrobées d'un copolymère tribloc qui accroît l'homogénéité en taille et en forme des nanoparticules métalliques enrobées d'un copolymère tribloc ; une quantité de nanoparticules métalliques enrobées d'un copolymère tribloc ; un procédé de production de nanoparticules métalliques modifiées qui accroît l'homogénéité en taille et en forme des nanoparticules métalliques modifiées, et ; une quantité de nanoparticules métalliques modifiées.
PCT/US2013/028422 2012-02-28 2013-02-28 Procédés de production, de modification et d'utilisation de nanoparticules métalliques WO2013130881A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US14/364,274 US9370490B2 (en) 2012-02-28 2013-02-28 Methods for the production, modification and use of metallic nanoparticles
US15/179,756 US20170119686A1 (en) 2012-02-28 2016-06-10 Methods for the production, modification and use of metallic nanoparticles

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261604354P 2012-02-28 2012-02-28
US61/604,354 2012-02-28

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US14/364,274 A-371-Of-International US9370490B2 (en) 2012-02-28 2013-02-28 Methods for the production, modification and use of metallic nanoparticles
US15/179,756 Continuation US20170119686A1 (en) 2012-02-28 2016-06-10 Methods for the production, modification and use of metallic nanoparticles

Publications (1)

Publication Number Publication Date
WO2013130881A1 true WO2013130881A1 (fr) 2013-09-06

Family

ID=49083308

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2013/028422 WO2013130881A1 (fr) 2012-02-28 2013-02-28 Procédés de production, de modification et d'utilisation de nanoparticules métalliques

Country Status (2)

Country Link
US (2) US9370490B2 (fr)
WO (1) WO2013130881A1 (fr)

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20010041991A1 (en) * 2000-02-09 2001-11-15 Segal Elliot A. Method and system for managing patient medical records
US6740338B1 (en) * 2000-01-20 2004-05-25 Raj K. Chopra Reduced form of Cenzyme Q in high bioavailability stable oral dosage form
RU2329074C1 (ru) * 2007-02-28 2008-07-20 Федеральное государственное образовательное учреждение высшего профессионального образования "Воронежский государственный аграрный университет имени К.Д. Глинки" (ФГОУ ВПО ВГАУ им. К.Д. Глинки) Способ лазерной деструкции меланомы слизистой рта у собак
US20080311207A1 (en) * 2004-09-08 2008-12-18 Manoj Varshney Micelles and Nanoemulsions for Preventive and Reactive Treatment of Atherosclerosis
US20090110642A1 (en) * 2007-10-31 2009-04-30 Kyoungja Woo Method for the production of bio-imaging nanoparticles with high yield by early introduction of irregular structure
US20090324494A1 (en) * 2006-02-24 2009-12-31 Atgen Co., Ltd Magnetic nano-composite for contrast agent, intelligent contrast agent, drug delivery agent for simultaneous diagnosis and treatment, and separation agent for target substance
WO2010120336A1 (fr) * 2009-04-15 2010-10-21 Poniard Pharmaceuticals, Inc. Thérapie anticancéreuse par voie orale à base de picoplatine à haute biodisponibilité
US20100323884A1 (en) * 2009-06-18 2010-12-23 University Of Central Florida Research Foundation, Inc. Thermally stable nanoparticles on supports
WO2011154711A1 (fr) * 2010-06-10 2011-12-15 Midatech Limited Nanoparticules portant des peptides
WO2011163136A2 (fr) * 2010-06-21 2011-12-29 University of Washington Center for Commercialization Nanoparticules magnétiques multifonctionnelles modulables pour la biomédecine
WO2012007567A1 (fr) * 2010-07-16 2012-01-19 Technical University Of Denmark Radiothérapie guidée par nanoparticules

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0903448D0 (en) * 2009-03-02 2009-04-08 Ct Angewandte Nanotech Can A method for the manufacture of nanoparticle complexes and triblock polymer ligands and products thereof

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6740338B1 (en) * 2000-01-20 2004-05-25 Raj K. Chopra Reduced form of Cenzyme Q in high bioavailability stable oral dosage form
US20010041991A1 (en) * 2000-02-09 2001-11-15 Segal Elliot A. Method and system for managing patient medical records
US20080311207A1 (en) * 2004-09-08 2008-12-18 Manoj Varshney Micelles and Nanoemulsions for Preventive and Reactive Treatment of Atherosclerosis
US20090324494A1 (en) * 2006-02-24 2009-12-31 Atgen Co., Ltd Magnetic nano-composite for contrast agent, intelligent contrast agent, drug delivery agent for simultaneous diagnosis and treatment, and separation agent for target substance
RU2329074C1 (ru) * 2007-02-28 2008-07-20 Федеральное государственное образовательное учреждение высшего профессионального образования "Воронежский государственный аграрный университет имени К.Д. Глинки" (ФГОУ ВПО ВГАУ им. К.Д. Глинки) Способ лазерной деструкции меланомы слизистой рта у собак
US20090110642A1 (en) * 2007-10-31 2009-04-30 Kyoungja Woo Method for the production of bio-imaging nanoparticles with high yield by early introduction of irregular structure
WO2010120336A1 (fr) * 2009-04-15 2010-10-21 Poniard Pharmaceuticals, Inc. Thérapie anticancéreuse par voie orale à base de picoplatine à haute biodisponibilité
US20100323884A1 (en) * 2009-06-18 2010-12-23 University Of Central Florida Research Foundation, Inc. Thermally stable nanoparticles on supports
WO2011154711A1 (fr) * 2010-06-10 2011-12-15 Midatech Limited Nanoparticules portant des peptides
WO2011163136A2 (fr) * 2010-06-21 2011-12-29 University of Washington Center for Commercialization Nanoparticules magnétiques multifonctionnelles modulables pour la biomédecine
WO2012007567A1 (fr) * 2010-07-16 2012-01-19 Technical University Of Denmark Radiothérapie guidée par nanoparticules

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
NIESZ ET AL.: "Precise Control of the Pt Nanoparticle Size by Seeded Growth Using EO13PO30EO13 Triblock Copolymers as Protective Agents.", NANO LETTERS., vol. 5, no. 11, 2005, Retrieved from the Internet <URL:http://www.mendeley.com/research/precise-control-pt-nanoparticle-size-seeded-growth-using-eo13po30eo13-triblock-copolymers-protective> [retrieved on 20130613] *

Also Published As

Publication number Publication date
US20140342005A1 (en) 2014-11-20
US20170119686A1 (en) 2017-05-04
US9370490B2 (en) 2016-06-21

Similar Documents

Publication Publication Date Title
Cheng et al. Nanomaterials for cancer therapy: current progress and perspectives
Fei et al. Targeted GSH-exhausting and hydroxyl radical self-producing manganese–silica nanomissiles for MRI guided ferroptotic cancer therapy
Marcato et al. New aspects of nanopharmaceutical delivery systems
CN100361651C (zh) 用于靶向药物送递和持续药物释放的静脉内纳米颗粒
Zhang et al. Formulation optimization of dihydroartemisinin nanostructured lipid carrier using response surface methodology
Nesalin et al. Preparation and evaluation of chitosan nanoparticles containing zidovudine
Asadipour et al. Nano‐biotechnology and challenges of drug delivery system in cancer treatment pathway
Yordanov et al. Epirubicin loaded to pre-polymerized poly (butyl cyanoacrylate) nanoparticles: preparation and in vitro evaluation in human lung adenocarcinoma cells
Krishna et al. Nanoparticles and their applications-a review
Lee et al. Gold-stabilized carboxymethyl dextran nanoparticles for image-guided photodynamic therapy of cancer
Liu et al. Self-assembled ultrasmall silver nanoclusters on liposome for topical antimicrobial delivery
KR20100000203A (ko) 금나노입자를 이용한 표적지향형 항암약물전달체
Jahan Nanotechnology for drug delivery and cancer therapy
Morad et al. Bioengineered metallic nanomaterials for nanoscale drug delivery systems
Britta et al. Generating nanoparticles containing a new 4-nitrobenzaldehyde thiosemicarbazone compound with antileishmanial activity
Severino et al. Advances in nanobiomaterials for oncology nanomedicine
US9370490B2 (en) Methods for the production, modification and use of metallic nanoparticles
Demirbolat et al. PEG4000 modified liposomes enhance the solubility of quercetin and improve the liposome functionality: in vitro characterization and the cellular efficacy
David et al. Gold nanoparticles in transferrin-targeted dual-drug delivery in vitro
Barbosa et al. Nanotechnology applied in drug delivery
US11938546B2 (en) Precision control of large-scale green synthesis of biodegradable gold nanodandelions as potential radiotheranostics
de Oliveira Machado et al. Development of a novel nano-biomaterial for biomedical applications
Nong et al. Growth regulation of luminescent gold nanoparticles directed from amphiphilic block copolymers: highly-controlled nanoassemblies toward tailored in-vivo transport
Sharma et al. Formulation and evaluation of polymeric nanomicelles of gliptin for controlled drug delivery
Jirofti et al. Lignin and Pluronic-based nanomicelles as promising amiodarone nanocarriers: Synthesis, physical characterization, biological, and in silico evaluations

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13754627

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 14364274

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13754627

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)